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Damage to the meniscus, bone marrow changes, and synovial activation are early knee OA pathogenic processes despite the prevailing concept that pathologic cartilage changes are an initiating event.

Specific early structural changes visible on MRI predicted the later development of radiographic osteoarthritis (OA), a nested case-control study found.

At 2 years before the diagnosis of OA could be made based on typical x-ray findings such as joint space narrowing, predictive MRI features included the presence of medial meniscal damage (HR 1.83, 95% CI 1.17-2.89), effusion synovitis (HR 1.81, 95% CI 1.18-2.78), and Hoffa synovitis (HR 1.76, 95% CI 1.18-2.64), according to Frank W. Roemer, MD, of Boston University School of Medicine, and colleagues.

Yet at that point cartilage damage -- long considered the pathogenic hallmark of OA -- was not associated with an increased risk of subsequent radiographic OA (HR 1.08, 95% CI 0.69-1.68), the researchers reported in the August Arthritis & Rheumatology.

"This finding emphasizes the role of noncartilaginous features in early disease as well as disease progression," they noted.

Despite the prevailing concept that pathologic changes in cartilage are an initiating event in knee OA, evidence to support this is lacking. In fact, recent studies have implicated damage to the meniscus, bone marrow changes, and synovial activation as early pathogenic processes.

In an editorial accompanying the study by Roemer and colleagues, Timothy E. McAlindon, MD, chief of rheumatology at Tufts Medical Center in Boston, argued against continuing with the paradigm of knee OA as being "primarily a degenerative disorder of hyaline articular cartilage."

He pointed out that cartilage is unlikely to be the source of pain in OA because of its aneural structure, and that it has little role in joint load mechanics, which is primarily transferred to periarticular bone.

"Considering the range of structures that are involved in OA pathology and the fact that many of them are more likely to contribute to pain and altered mechanics, it is perhaps surprising that hyaline cartilage has instead been viewed as the hallmark of OA," McAlindon wrote.

"It is clear that we need to change the construct of OA as we teach it to students, trainees, and colleagues. That old paradigm has arguably stifled research and progress in this field for decades," he stated.

To explore the preradiographic findings in knee OA, Roemer and colleagues utilized the Osteoarthritis Initiative, which is an ongoing longitudinal study that is seeking to identify biomarkers of disease initiation and progression. The cohort includes almost 5,000 individuals considered to be at risk for OA who had both radiographs and MRIs of their knees done at baseline and then 1, 2, 3, and 4 years later.

The study included 355 "case knees" and 355 matched control knees. The case knees were those in which radiographic OA developed during the 4-year follow-up.

Participants' mean age was 60, and two-thirds were women. Most were overweight.

At 1 year before the onset of radiographic OA, there were many structural changes that predicted incident radiographic OA, with the strongest risk factors being:

Medial bone marrow lesions, HR 6.50 (95% CI 2.27-18.62)

Tibiofemoral bone marrow lesions, HR 3.70 (95% CI 1.84-7.44)

Effusion synovitis, HR 2.50 (95% CI 1.76-3.54)

And even as early as 4 years before OA radiographic diagnosis, there were trends (though not significant) toward prediction for some markers such as Hoffa synovitis (HR 1.91, 95% CI 0.91-4).

The researchers also considered the effects of the number of positive MRI findings, and found that having five or six structural changes 2 years before diagnosis was associated with a six-fold increased risk of incident OA, while having five or six features 1 year before diagnosis raised the risk almost 12-fold.

"The fact that cartilage damage played a lesser role in incident OA in our analyses supports the strategy of targeting the subchondral bone in early disease as an important treatment approach," Roemer and colleagues wrote.

"The field of knee OA is at a tipping point predicated on determining which pathologies come first and how the disorder progresses," McAlindon wrote in his editorial.

However, prevention remains important, as was emphasized by Eric Matteson, MD, chair of rheumatology at the Mayo Clinic in Rochester, Minn., who was not involved in the study.

"From a practical standpoint, I think the implications of the study are that because OA is so common, and joint changes occur over time and eventually may become symptomatic, everyone should endeavor to reduce risk for developing clinical symptomatic OA," Matteson told MedPage Today.

"This includes weight loss and strengthening of the lower extremities," he added.

A limitation of the study was the lack of information on patient symptoms.

The study was supported by the Osteoarthritis Initiative, which is a partnership between the National Institutes of Health and private funders including Merck, Novartis, GlaxoSmithKline, and Pfizer.

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